Js. Nowick et al., AN EXTENDED BETA-STRAND MIMIC FOR A LARGER ARTIFICIAL BETA-SHEET, Journal of the American Chemical Society, 119(23), 1997, pp. 5413-5424
This paper reports the development of beta-strand mimic B, which dupli
cates the hydrogen-bonding functionality of one edge of a tetrapeptide
beta-strand. When attached to a tripeptide by a suitable Linking grou
p, beta-strand mimic B forms a hydrogen-bonded antiparallel beta-sheet
structure, artificial beta-sheet 2. beta-Strand mimic B is based upon
a 5-hydrazino-2-methoxybenzoic acid building block. The first half of
the paper describes synthetic, IR and H-1 NMR spectroscopic, X-ray cr
ystallographic, and molecular modeling studies of 5-hydrazino-2-methox
ybenzoic acid derivatives and related molecules. These studies establi
sh that hydrazide derivatives of 5-hydrazino-2-methoxybenzoic acid ado
pt a conformation similar to that of a peptide beta-strand and are sui
table for use as beta-strand mimics. The second half of the paper desc
ribes synthetic and H-1 NMR spectroscopic studies of artificial beta-s
heet 2 and of controls 20 and 21, which resemble the peptidomimetic an
d peptide strands of 2. These experiments indicate that 2 adopts a con
formation and hydrogen-bonding pattern similar to that of an antiparal
lel beta-sheet and establish that beta-strand mimic B can induce beta-
sheet formation in an attached peptide strand.